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PubMed2026

Maternal prior pregnancy outcome subtype and offspring cryptorchidism: A retrospective case-control study.

OBJECTIVE: To determine whether maternal prior pregnancy outcome subtype and frequency are associated with cryptorchidism in male offspring, and whether first-trimester exogenous progesterone exposure mediates any observed association. MATERIALS AND METHODS: We conducted a hospital-based retrospective case-control study of 1220 mother-son pairs (610 cryptorchidism cases; 610 controls). Maternal prior pregnancy outcome subtype was defined using a prespecified proximal-event approach based on the most recent qualifying pregnancy event before the index pregnancy: no prior pregnancy loss or termination, miscarriage, or pregnancy termination. Subtype-specific frequency was categorized as 0, 1, or ≥2. Adjusted odds ratios (aORs) were estimated using multivariable logistic regression; robustness was examined using 1:1 propensity score matching with conditional logistic regression. Exploratory mediation analysis estimated indirect effects through first-trimester exogenous progesterone exposure. RESULTS: In fully adjusted models, miscarriage was associated with higher odds of cryptorchidism compared with no prior pregnancy loss or termination (aOR 1.97; 95% CI 1.26-3.09), whereas pregnancy termination was not (aOR 1.14; 95% CI 0.86-1.52). In joint subtype-frequency analyses, odds increased with the number of miscarriages (one: aOR 1.74; 95% CI 1.07-2.83; two or more: aOR 3.77; 95% CI 1.22-11.66) and were higher for two or more pregnancy terminations (aOR 1.77; 95% CI 1.10-2.84). Matched analyses were directionally consistent. Mediation analyses suggested a modest indirect effect through first-trimester progesterone exposure for the miscarriage association. CONCLUSIONS: Maternal prior miscarriage was associated with cryptorchidism in male offspring, whereas pregnancy termination showed higher odds only among women with two or more prior procedures. First-trimester exogenous progesterone exposure may account for a modest proportion of the miscarriage-cryptorchidism association.

Humans↗

PubMed2026

Obstructive sleep apnea and idiopathic intracranial hypertension: a systematic review and meta-analysis.

OBJECTIVE: To determine the pooled prevalence of obstructive sleep apnea (OSA) among adults with idiopathic intracranial hypertension (IIH) using polysomnography (PSG) and the Berlin Questionnaire screening. NATURE: IIH is a vision-threatening disorder characterized by elevated intracranial pressure. OSA shares overlapping risk factors and pathophysiological mechanisms with IIH, including nocturnal hypoxia and hypercapnia. Clarifying OSA prevalence in IIH is clinically important for diagnosis and management. METHODS: For this prospectively registered systematic review and meta-analysis (PROSPERO: CRD420251132794), we searched MEDLINE, Embase, and CENTRAL from inception to August 23, 2025, for studies reporting PSG-confirmed OSA or Berlin Questionnaire positivity in adults with IIH. Risk of bias was assessed using ROBINS-I and RoB-2, and certainty of evidence was checked using the Grading of Recommendations, Assessment, Development and Evaluation tool. Random-effects meta-analyses of proportions generated pooled prevalence estimates. Subgroup analyses excluded high-risk studies, leave-one-out analyses assessed robustness, and funnel plots evaluated publication bias. RESULTS: Eleven studies met the inclusion criteria. Across 9 PSG-based studies (n = 299), the pooled prevalence of OSA in IIH was 0.44 (95% CI: 0.26-0.63; I² = 90.5%). Leave-one-out analyses showed stable results (39%-50%). Excluding high-risk studies (4 studies; n = 132) yielded a pooled prevalence of 0.53 (95% CI: 0.32-0.74). Four Berlin Questionnaire studies (n = 154) showed a pooled prevalence of 0.65 (95% CI: 0.54-0.74; I² = 0%). Funnel plot asymmetry suggested publication bias, and certainty of evidence was very low. CONCLUSIONS: OSA is common among patients with IIH, supporting routine objective sleep evaluation. Prospective studies are needed to clarify this association.

Humans↗

PubMed2026

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus↗

PubMed2026

The potential of clustering methods for pre-test triage in sleep medicine: A systematic review.

Sleep disorders exhibit substantial heterogeneity, and traditional classifications may not fully capture clinically relevant subtypes. Clustering techniques can identify patient subgroups that improve phenotypic characterization and may support personalized management. This systematic review evaluated the application of clustering in sleep medicine, with particular focus on its potential use as a pre-test triage tool prior to formal sleep testing. PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched to February 2025. Eligible studies applied clustering to classify sleep disorders in adults. Two reviewers independently conducted screening, data extraction, and risk-of-bias assessment using QUADAS-2. The protocol was registered on PROSPERO. Fifty-one studies (1983-2025) were included, predominantly focused on obstructive sleep apnea (OSA) (n = 38, 74%). Hierarchical clustering (n = 20) and K-means clustering (n = 14) were the most frequently used techniques. Internal validation was reported in only 18% of studies, and external validation was reported in only 1 study. Seven studies relied exclusively on baseline clinical, demographic, or questionnaire data, representing pre-test scenarios, whereas most incorporated polysomnography-derived variables, limiting their applicability to early clinical stratification. Hierarchical clustering was the most commonly applied method; however, the overall lack of validation limits confidence in the robustness and clinical applicability of identified phenotypes. The potential role of clustering as a pre-test triage strategy remains largely unexplored, as most studies focused on post-diagnostic phenotyping and were affected by incorporation bias. Future research should prioritize pre-test clinical variables, rigorously validate internally and externally, and adopt standardized methodological and reporting practices to facilitate clinical translation.

Humans↗

PubMed2026

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans↗

PubMed2026

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (0.9% saline) 24 h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96 h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n = 73) or placebo (n = 83). Psychological pain decreased in both groups but was lower with ketamine during the first 96 h. Pointwise scores were lower with ketamine from 40 min to 96 h, largest at 40 min, 2 h, 4 h, and 24 h (all p < 0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96 h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

Humans↗

PubMed2025

Mediators of the Association Between a Parent's Experience of Trauma and Their Children's Well-Being: A Systematic Review.

At present, our understanding of trauma's complexity is underdeveloped, particularly with regard to intergenerational effects. In this paper, we review peer-reviewed literature on parental trauma and child well-being, focusing on mediating factors. We conducted a global systematic review of longitudinal, observational studies assessing mediators between a parent's traumatic exposure and their children's well-being. The primary outcome of the review was quantitative measures of child well-being (physical and psycho-social) assessed when the child was 18 years or under. We considered the following experiences as trauma exposures: intimate partner violence, rape, sexual assault, victimization during violent crime, childhood abuse, and exposure to direct, immediate threats to personal survival during war, political unrest, natural disasters, and sudden, critical injury/illness. Thirty-two studies met our inclusion criteria. The two most common mediator categories were caregiver mental health (n = 13) and parenting behavior (n = 10). Other studies measured aspects of the parent-child relationship (n = 9), maternal stress factors (n = 5), parental physical health (n = 2), and child-level factors (n = 6) as mediators. Almost all included studies (n = 28) detected a mediation effect. The majority of studies (n = 21) cited robust theoretical frameworks to support their mediator and outcome choices. Studies varied in quality, but most used appropriate, formal mediation analyses. Several study designs could be enhanced by methods to improve precision and reduce bias. Currently, there is little consistency in how similar constructs are measured between mediation studies. We did not locate any studies in low-income countries, and few studies examined aspects of family dynamics, physical health, environmental characteristics, or paternal factors.

Humans↗

PubMed2026

Ventriculostomy-Related Infections by Country-Income Level: A Systematic Review and Bayesian Hierarchical Meta-analysis.

Our objective was to perform a systematic review and meta-analysis of published literature on ventriculostomy-related infection (VRI) and evaluate temporal and global trends. We conducted a systematic review and Bayesian hierarchical random-effects meta-analysis of VRI rates in adults, stratified by country-income level (high-income countries [HIC]; low- or middle-income countries [LMIC]), study design, sample size, enrollment period, VRI intervention, and VRI definition. We identified 159 articles published between 1989 and 2025 that included 523,704 patients with 7293 VRIs. The pooled VRI rate was 8.64% [95% CI: 7.44-9.97], with moderate heterogeneity and good model fit. The leave-one-out sensitivity analysis showed a mean absolute change of 0.06% and a maximum change of 0.2%, indicating robust analysis. Five of the 33 represented countries had VRI rates below the global pooled rate of 8.64%. Four were HICs: Singapore (VRI rate 3.3% [0.8-7]), the United States (VRI rate 4.6% [3.4-5.9]), Germany (VRI rate 6.1% [1.1-18.9]), Norway (8.3% [0.3-68.4]), with 1 LMIC: China (8.5% [5.4-12.4]). VRI was significantly higher in studies using definitions beyond CSF culture alone for VRI (+3.16% [0.11- 6.52]) and in those from Europe (+7.29% [4.62-10.10]) and the Western Pacific (+4.09% [1.55-6.98]). No other subgroup demonstrated significant differences. This Bayesian meta-analysis provides global estimates and factors associated with VRI. Standardization of VRI definitions is critical for future benchmarking of VRI rates.

Humans↗

PubMed2026

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE + six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals↗

PubMed2026

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2↗

PubMed2026

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2026

Exercise-induced chronic adaptations and pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in patients with depression: A systematic review and exploratory meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a leading cause of disability worldwide. Although exercise has been shown to alleviate depressive symptoms, potentially by affecting the body's inflammatory response, evidence in this area remains inconsistent. This study synthesized the most recent evidence from randomized controlled trials (RCTs) on the relationship between exercise-induced chronic adaptations and pro-inflammatory cytokine levels in patients with depression. METHODS: Eligible RCTs were identified from six electronic databases. Effect sizes were pooled using mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Two independent researchers assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: The review included 21 RCTs involving 1572 participants, six of which were included in the meta-analysis. No evidence of efficacy was observed for the chronic effects of exercise on the levels of the pro-inflammatory cytokines interleukin-1-beta (IL-1β) (MD = -0.01, 95% CI [-0.06, 0.04], p = 0.79), interleukin-6 (IL-6) (SMD = -0.30, 95% CI [-0.64, 0.04], p = 0.08), and tumor necrosis factor-alpha (TNF-α) (SMD = -0.18, 95% CI [-0.50, 0.14], p = 0.27) in patients with depression. However, the pooled results for certain markers were not robust. The certainty of evidence for each outcome was very low owing to inconsistency, indirectness, and imprecision. CONCLUSIONS: Evidence for exercise improving pro-inflammatory cytokine levels in patients with depression during the chronic phase remains exploratory and uncertain. Well-designed, adequately powered studies incorporating a broader range of immune biomarkers and dynamic multi-time-point assessments are urgently needed to determine whether exercise-induced chronic adaptations can modulate inflammatory pathways in depression.

Humans↗

PubMed2026

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA↗

PubMed2026

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans↗

PubMed2026

Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors.

From pre-formulation studies to clinical trials, VEGFR-targeted small-molecule tyrosine kinase inhibitors (TKIs) require rigorous analytical standards. Bioanalysis, stability-indicating studies, and impurity profiling are used to examine chromatographic advances for VEGFR-targeted TKIs like sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, vandetanib, apatinib, lenvatinib, nintedanib, and regorafenib. An LC-MS/MS and UPLC-MS/MS routinely show sub ng/mL performance, as shown by LLOQs (0.2 ng/mL) for sunitinib and axitinib, 1 ng/mL for pazopanib, 5-7 ng/mL for sorafenib, 0.5-1.5 ng/mL for regorafenib metabolic products, and 0.1-0.5 ng/mL for lenvatinib. These approaches are used for pharmacokinetics and therapeutic drug monitoring due to their good correlation coefficient of 0.1-10,000 ng/mL, accuracy of 95%-108%, and precision of 15% RSD. UPLC-QTOF-MS/MS distinguishes degradants and metabolites during forced degradation studies, enabling structural elucidation following ICH M7 risk evaluation protocol. HPTLC/MLC offers fast, sensitive screenings, while RP-HPLC/DAD or HPLC-UV offer reliable, cost-effective routine quality-control solutions with LOD/LOQ in the μg/mL range and linearity of 10-240 μg/mL. This review lists the structures and CAS numbers of ten VEGFR-2 TKI degradants and metabolites, as well as pharmacopeial impurities in SMILES forms. It will be useful for future method development and regulatory applications. To ensure VEGFR-targeted TKI quality, safety, and therapeutic efficacy, LC-MS/MS for trace quantification and HRMS for structure elucidation provide a robust, future-oriented framework. To improve VEGFR-targeted TKI quality, safety, and regulatory compliance, analytical development should focus on HRMS-based impurity characterization, AI-assisted degradation prediction, green chromatography, and harmonized bioanalytical validation.

Humans↗

PubMed2026

Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

Humans↗

PubMed2026

Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value. METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool. RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181. CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.

Humans↗

PubMed2026

Efficacy and safety of middle meningeal artery embolization for chronic subdural hematoma: an updated systematic review and meta-analysis focusing on time of intervention.

INTRODUCTION: Chronic subdural hematoma (cSDH) is increasingly prevalent among older adults due to population aging and widespread antithrombotic use. Although burr-hole drainage remains the standard treatment, recurrence rates are substantial. Middle meningeal artery embolization (MMAE) has emerged as an adjunctive strategy to disrupt dural neovascularization and prevent rebleeding. OBJECTIVES: To assess the efficacy and safety of MMAE combined with standard therapy versus standard therapy alone, with stratification by timing of intervention. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Scopus, and Cochrane Central up to July 2025. Adults with confirmed cSDH were included. The primary outcome was hematoma recurrence or persistence. Secondary outcomes were reoperation, hematoma resorption, serious adverse events, neurological death, mortality, functional independence, and hospital stay. Risk of bias was assessed with RoB-2, and analyses followed PRISMA guidelines (PROSPERO CRD420251112841). RESULTS: Seven RCTs (1,889 patients) were included. Compared with standard therapy, MMAE significantly reduced recurrent or residual cSDH (RR 0.63; 95% CI 0.46-0.85) and reoperation (RR 0.39; 95% CI 0.28-0.56) without increasing serious adverse events (RR 0.87; 95% CI 0.72-1.06), neurological death, mortality, or poor functional outcomes. Hematoma resorption did not differ significantly. Subgroup and sensitivity analyses confirmed the robustness of the results across age, intervention timing, and follow-up duration. CONCLUSION: MMAE combined with standard therapy significantly reduces recurrence and reoperation in cSDH without increasing adverse events or mortality. Benefits appear independent of procedural timing, though larger RCTs with extended follow-up are warranted to define long-term outcomes and optimal use.

Humans↗